Synergistic antibacterial effects of magnolia bark extract and L-arginine, Nα-lauroyl ethyl ester on salivary bacteria

ABSTRACT

The present disclosure relates generally to oral compositions and methods for oral cleansing and reducing salivary bacteria, and more particularly, to oral compositions comprising a combination of magnolia bark extract (MBE) and L-arginine, Nα-lauroyl ethyl ester (LAE). The oral compositions are useful for improving oral health, including freshening breath and reducing total salivary bacteria.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.62/217,212, filed Sep. 11, 2015, which is herein incorporated byreference in its entirety.

BACKGROUND OF THE DISCLOSURE

The present disclosure relates generally to oral compositions andmethods for oral cleansing and reducing salivary bacteria, and moreparticularly, to oral compositions comprising a combination of magnoliabark extract (MBE) and L-arginine, N^(α)-lauroyl ethyl ester (LAE). Theoral compositions are useful for improving oral health, includingfreshening breath and reducing total salivary bacteria.

The oral cavity is comprised of more than 700 bacterial species (Aas, etal., “Defining the normal bacterial flora of the oral cavity,” J. Clin.Microbiol., 2005, Vol. 43(11), pp. 5721-32) that live together insymbiosis at times of good oral health (Zarco, et al., “The oralmicrobiome in health and disease and the potential impact onpersonalized dental medicine,” Oral. Dis., 2012, Vol. 18(2), pp.109-20). An ecological shift in the oral microbiome, due to variousextrinsic or intrinsic stimuli, can result in an abundance of certainpathogenic bacterial strains and cause oral disease, such as caries,gingivitis, and/or halitosis. The key to maintenance of oral health ismaintaining the symbiotic nature of the oral microbiome and preventingovergrowth of pathogenic species within the oral biofilm. This islargely achieved by regular oral hygiene, such as tooth brushing, whichmechanically removes the oral biofilm. Dental floss, toothpicks, mouthrinses, and chewing gum have also been promoted as adjuncts to regularoral hygiene (see Imfeld, T., “Chewing gum-facts and fiction: A reviewof gum-chewing and oral health,” Crit. Rev. Oral Biol. Med., 1999, Vol.10(3), pp. 405-19; Crocombe, et al. “Is self interdental cleaningassociated with dental plaque levels, dental calculus, gingivitis andperiodontal disease?” J. Periodontal Res., 2012, Vol. 47(1), pp.188-97).

Dental plaque is a highly complex biofilm consisting of over 300microbials, their metabolites, and salivary pellicles that form on theteeth within a short time after brushing. One of the challenges inpreventing the formation of dental plaque lies in the nature of plaquebiofilm. In particular, plaque biofilm has a complex structure thatprotects salivary bacteria from xenobiotics (Marsh, P. D. (2004).“Dental plaque as a microbial biofilm” Caries Research, 38(3):204-211).The complexity of the biofilm structure limits diffusion ofantimicrobials into the biofilm matrix, resulting in protection ofbacteria within the biofilm from exposure to the antimicrobial agent. Inaddition, it has been suggested that bacteria in plaque biofilm formsymbiotic relationships to protect each other by metabolizing substancesthat threaten other microbials in the biofilm (Busscher H. J., Evans L.V., Editors. 1998. “Oral Biofilms and Plaque Control,” CRC Press. ISBN978-90-5702-391-0). Thus, it is easier to prevent formation of plaquethan to remove an established plaque. To either remove or penetrate anexisting biofilm, it may be necessary to use surfactants, abrasives,enzymes or other agents that would aid in the penetration and removal ofthe plaque.

Two major mechanisms of action for plaque prevention are: 1)anti-microbial agents and 2) glucosyl transferase (GTF) inhibition.Antimicrobial agents that have been shown to have definiteplaque-reducing abilities include chlorhexidine, cetylpyridiniumchloride (CPC), triclosan and delmopinol. These are all medicinal andnon-natural antimicrobial agents. Essential oils such as thymol,eucalyptol, methyl salicylate, and menthol along with other essentialoils in an alcohol-based vehicle have also been found to reduce plaque.While thymol is most effective in reducing plaque, it has a disagreeabletaste. Generally, these oils benefit from the presence of an alcohol tofacilitate their solubility and penetration of the plaque biofilm.Furthermore, while suitable for oral treatments, such as mouthwashes,high concentrations of alcohols can leave a bitter aftertaste in oralcompositions, such as gums, mints, edible films, confectioneries, andthe like. While there are several GTF inhibitors reported in scientificpublications and patents, their potential for use in oral compositionsand confections has not been tested.

There is thus a need for other oral compositions that can be used tofacilitate removal of bacteria from the oral cavity and prevent orreduce the formation of plaque. It would be particularly advantageous tohave an oral composition that promotes oral health, and morespecifically, that targets oral bacteria responsible for oral healthissues, such as plaque formation and halitosis.

SUMMARY OF THE DISCLOSURE

The present disclosure relates generally to oral compositions andmethods for oral cleansing and reducing salivary bacteria, and moreparticularly, to oral compositions comprising a combination of magnoliabark extract (MBE) and L-arginine, N^(α)-lauroyl ethyl ester (LAE). Theoral compositions are useful for improving oral health, includingfreshening breath and reducing total salivary bacteria.

Thus, in one aspect, the present disclosure is directed to an oralcomposition for reducing total salivary bacteria in an oral cavity of aconsumer, the composition comprising MBE and LAE, wherein the oralcomposition comprises the MBE and LAE in amounts that provide asynergistic reduction of the total salivary bacteria in the oral cavity.In various embodiments, the oral composition may comprise MBE and LAE ina weight ratio of from about 2:1 to about 1:2.

In another aspect, the present disclosure is directed to a coated oralcomposition for reducing total salivary bacteria in an oral cavity of aconsumer, the coated oral composition comprising MBE and LAE in amountsthat provide a synergistic reduction of the total salivary bacteria inthe oral cavity.

In another aspect, the present disclosure is directed to a method ofmaking a coated oral composition, the method comprising: pretreating MBEand LAE to form a preblend mixture; adding the preblend mixture to acoating syrup; and, applying the coating syrup to an oral composition toproduce the coated oral composition. In various embodiments, thepretreating may comprise sieving the MBE and LAE, sonicating the MBE andLAE, and/or blending the MBE and LAE with one or more organolepticcomponents.

In another aspect, the present disclosure is directed to a method ofmaking a chewing gum composition, the method comprising: pretreating MBEand LAE to form a preblend mixture; and forming the chewing gumcomposition from the preblend mixture. In various embodiments, thepretreating may comprise sieving the MBE and LAE, sonicating the MBE andLAE, and/or blending the MBE and LAE with a powdered gum base.

In another aspect, the present disclosure is directed to a method forreducing the total salivary bacteria in an oral cavity of a mammaliansubject, the method comprising: contacting an oral composition of thepresent disclosure with the oral cavity of the subject.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph depicting the effect of chewing gum on the acidproduction of plaque bacteria. Plaque bacteria was collected before(“pre treatment”) and after (“post treatment”) chewing of an MBE/LAEcontaining gum (“MBE gum”), a control gum containing no MBE or LAE(“control gum”), or a gum base containing no MBE or LAE. FIG. 1 showsthe average pH of dispersions of the plaque biomass obtained at time ofplaque collection (0 hour), or after 2 or 4 hours of incubation.

FIG. 2 is a graph depicting the change in acid production (representedas difference in pH, “ΔpH”) of plaque bacteria 2 and 4 hours afterchewing (“post”) of an MBE/LAE containing gum (“MBE gum”), a control gumcontaining no MBE or LAE (“control gum”), or a gum base containing noMBE or LAE. The change in acid production over time of plaque bacteriacollected before (“pre”) chewing is also depicted.

FIG. 3 is a graph depicting the effect of chewing gums on the regrowthof plaque bacteria (expressed as regrowth ratios, OD_(final/intial)) insix test subjects 2 and 4 hours after chewing (“post”) of an MBE/LAEcontaining gum (“MBE gum”), a control gum containing no MBE or LAE(“control gum”), or a gum base containing no MBE or LAE. The regrowthover time of plaque bacteria collected before (“pre”) chewing is alsodepicted.

FIG. 4 is a graph depicting the average regrowth ratios of plaquebacteria 2 and 4 hours after chewing (“post”) of an MBE/LAE containinggum (“MBE gum”), a control gum containing no MBE or LAE (“control gum”),or a gum base containing no MBE or LAE. The regrowth over time of plaquebacteria collected before (“pre”) chewing is also depicted.

DETAILED DESCRIPTION OF THE DISCLOSURE

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which the disclosure belongs. Although any methods andmaterials similar to or equivalent to those described herein can be usedin the practice or testing of the present disclosure, the preferredmaterials and methods are described below.

The present disclosure relates generally to oral compositions andmethods for oral cleansing and reducing salivary bacteria. Moreparticularly, the present disclosure relates to oral compositionscomprising a combination of magnolia bark extract (MBE) and L-arginine,N^(α)-lauroyl ethyl ester (LAE). The oral compositions are useful forimproving oral health, including freshening breath and reducing totalsalivary bacteria.

Surprisingly, it has been discovered that MBE in combination with LAE issynergistically effective at reducing total salivary bacteria. As usedherein, “synergy” or “synergistic effect” refers to the effect thatoccurs when chemical substances or biological structures interact, andresult in an overall effect that is greater than the sum of individualeffects of any of them. This combination thus greatly improves andfacilities the reduction of salivary bacteria in the oral cavity of aconsumer. Incorporating the combination of an effective amount of MBEand LAE into an oral composition can thus provide an oral compositionthat synergistically reduces or diminishes the amount of the totalsalivary bacteria. The oral compositions of the present disclosure mayalso be effective for use in inhibiting plaque formation and in theremoval of existing plaque, and in reducing halitosis associated withcertain salivary bacteria.

As used herein, the term “efficacious” means producing or capable ofproducing a desired effect. Moreover, “effective amount” or “effectiveconcentration” refers to the level, amount, serving, or percent whichproduces or is capable of producing a desired effect. All percentagesand ratios used herein are by weight of the total composition and allmeasurements made are at 25° C., unless otherwise designated.

In another aspect, the present disclosure is directed to a method forreducing total salivary bacteria in an oral cavity of a mammaliansubject. The method comprises contacting a composition of the presentdisclosure with the oral cavity of said subject. The mammalian subjectmay be human or a non-human animal.

In still another embodiment, the present disclosure is directed to amethod of making a coated oral composition. The method comprisespretreating MBE and LAE to form a preblend mixture, adding the preblendmixture to a coating syrup, and applying the coating syrup to an oralcomposition to produce the coated oral composition. The MBE and LAE maybe pretreated by sieving the MBE and LAE prior to addition to thecoating syrup; sonicating the MBE and LAE prior to addition to thecoating syrup; blending the MBE and LAE with one or more organolepticcomponents prior to addition to the coating syrup; or combinationsthereof.

In still other embodiments, the present disclosure is directed to amethod of making a chewing gum composition. The method comprisespretreating MBE and LAE to form a preblend mixture, and forming thechewing gum composition from the preblend mixture. The MBE and LAE maybe pretreated by sieving the MBE and LAE; sonicating the MBE and LAE;blending the MBE and LAE with a powdered gum base; or combinationsthereof.

Without wishing to be bound to any particular theory, it is believedthat pretreating the MBE and LAE results in an improved loadingefficiency and release rate of the MBE from the oral composition, ascompared to oral compositions comprising MBE alone, or compositionscomprising MBE and LAE that are not pretreated. In particular, incertain embodiments, pretreating by sieving the actives and sonicatingresults in a loading efficiency of greater than 90% in conventionalchewing gums. Pretreating thus improves loading efficiency in chewinggum from about 50% to about 90%.

Magnolia Bark Extract

The compositions of the present disclosure comprise extract of magnolia(also referred to herein as “magnolia extract,” “magnolia bark extract,”or “MBE”). As referred to herein, such an “extract” of magnolia is anextract from dried cortex, or bark, of a plant from the Magnoliaceaefamily, such as Magnolia officinalis, (“magnolia”) or a synthetic orsemi-synthetic equivalent of such an extract or an active component orcompound thereof. Typically, extracts of Magnolia Cortex (the bark ofMagnolia officinalis) contain hydrophobic compounds including magnolol,honokiol, tetrahydromagnolol, and tetrahydrohonokiol. Any plant from theMagnoliaceae family is suitable for the present invention and may beused in alternate embodiments, preferably such that the extractcomprises an effective concentration of a compound selected from thegroup consisting of magnolol, honokiol, tetrahydromagnolol,tetrahydrohonokiol, and combinations thereof, and preferably aneffective concentration of magnolol and/or honokiol. Preferably, theeffective concentration of magnolia extract (or an active(s) therein) isa concentration that results in a reduction of total salivary bacteriawhen used in combination with LAE. Preferably, the effectiveconcentration of magnolia extract is such that a synergistic reductionin total salivary bacteria is achieved when the magnolia extract is usedin combination with LAE.

As used herein, “extracting” or “extraction” of a solid or liquidmaterial means contacting the material with an appropriate solvent toremove the substance(s) desired to be extracted from the material. Wherethe material is solid, it is preferably dried and crushed or groundprior to contacting it with the solvent. Such an extraction may becarried out by conventional means known to one of skill in the art, forexample, by using an extraction apparatus, such as a Soxhlet apparatus,which retains the solid material in a holder and allows the solvent toflow through the material; or by blending the solvent and materialtogether and then separating the liquid and solid phases or twoimmiscible liquid phases, such as by filtration or by settling anddecanting.

In one embodiment, magnolia extract is made from dried Magnolia plantbark and can be prepared by extracting the bark using an appropriatesolvent. Solvents include compatible liquids such as hydrocarbons andsubstituted hydrocarbons.

In preferred embodiments, the natural extract active ingredients used inoral compositions are reproducible, stable, and have microbiologicalsafety. In one embodiment of the present invention, the magnolia extractis isolated by supercritical fluid extraction (SFE) using carbon dioxide(CO₂). Supercritical fluids use a solvent that is readily available,inexpensive, and environmentally safe (such as CO₂). Carbon dioxide isnon-toxic, non-explosive, readily available and easily removed from theextracted products.

In certain embodiments, SFE extraction produces a much lighter color ofmagnolia extract (a light beige product) that is particularly suitablefor aesthetically pleasing oral composition formulations.

In various embodiments, it is preferred that the active ingredient inthe magnolia extract comprises either magnolol, honokiol, or both.Magnolol and honokiol are non-ionic hydroxybiphenyl compounds, thestructures of which are believed to be as follows:

Additionally, tetrahydromagnolol and tetrahydrohonokiol are hydrogenatedanalogs of magnolol and honokiol often found in relatively smallconcentrations in the extracts of magnolia, and as such may be includedin the composition.

Thus, as will be described in greater detail below, in variousembodiments of the present invention, the magnolia extract comprises oneor more hydrophobic compounds: magnolol, honokiol, tertrahydromagnolol,tetrahydrohonokiol, and mixtures thereof, which are used in combinationwith LAE to reduce salivary bacteria present in the oral cavity.

In various embodiments, magnolia extract of the present inventioncomprises magnolol, honokiol, or both in an amount of about 2% to about99% by weight. In other embodiments, magnolia extract comprisesmagnolol, honokiol, or both in an amount greater than 50% by weight. Inone embodiment of the present invention, the magnolol is present in anamount greater than 50% by weight, preferably greater than 70% byweight, or most preferably, greater than 90% by weight. In anotherembodiment, honokiol is present in an amount less than 50% by weight,more preferably in an amount less than 30% by weight, or, mostpreferably, less than 10% by weight.

The MBE may be present in the oral composition in an amount of from0.001 to about 10% by weight. In some embodiments, the MBE is present inthe oral composition in an amount of about 0.001 to about 5.0% byweight, or about 0.001 to about 2.0% by weight. In another embodiment,the MBE is present in the oral composition in an amount of about 1.0 toabout 2.0% by weight. In other embodiments, the MBE is present inamounts less than 1% by weight, for example the MBE may be present inthe oral composition in an amount of from about 0.01 to about 1% byweight. In a preferred embodiment, the MBE is present in an amount fromabout 0.01 to 0.5% by weight. Most preferably, the MBE is present in theoral compositions in an amount sufficient to provide a synergisticweight ratio of the MBE to the LAE in the composition. In particular,the MBE is preferably present in the oral compositions in combinationwith LAE in an amount sufficient to result in a synergist reduction inthe total salivary bacteria in the oral cavity of a consumer of the oralcomposition.

In various embodiments, the oral compositions will comprise from about 1to about 20 mg of MBE. In another aspect, the oral compositions willcomprise from about 1 to about 10 mg of MBE.

L-Arginine, N^(α)-Lauroyl Ethyl Ester

In addition to the MBE, the oral compositions of the disclosure furthercomprise L-Arginine, N^(α)-Lauroyl Ethyl Ester (LAE). LAE is also knownas lauric arginate ethyl ester, lauramide arginine ethyl ester,N-lauroyl-L-arginine ethyl ester, ethyl-N^(α)-lauroyl-L-arginate.HCl,and INS No. 243. It is a cationic amino acid derivative that may be usedas a food preservative. LAE has bacteriostatic activity against Grampositive bacteria, Gram negative bacteria, molds, yeasts, and other foodspoilage microorganisms (see Rodriguez, E., et. al, “Cellular effects ofmonohydrochloride of L-arginine, N^(α)-lauroyl-ethyl ester (LAE) onexposure to Salmonella typhimurium and Staphylococcus aureus”, J.Applied Microbio., 2004, Vol. 96(5), 903-912). LAE is a derivative oflauric acid, L-arginine, and ethanol, and metabolism of LAE yieldsL-arginine, ethanol, and lauric acid, which are three common componentsof a normal diet (see Ruckman, S., et. al, “Toxicological and metabolicinvestigations of the safety of N^(α)-lauroyl ethyl estermonohydrochloride (LAE)”, Food and Chemical Toxicology, 2004, Vol. 42,245-259).

The neutral, non-salt form of LAE is shown below:

LAE may form both neutral and cationic salts. As used herein, “LAE” isintended to cover both the salt and neutral forms, unless otherwiseindicated.

In some embodiments, the LAE is food grade and is suitable for use as afood additive. It has been designated by the United States FDA asgenerally regarded as safe (GRAS) or FEMA GRAS (Intl. Flavor Manuf.Assoc.). In one non-limiting example, LAE is the cationicmonohydrochloride salt. LAE is commercially available, and is sold underthe trade name MIRENAT®-P/100 by Vedeqsa of Barcelona, Spain.

The LAE is present in the oral composition in an amount of from 0.001 toabout 10% by weight. In some embodiments, the LAE is present in the oralcomposition in an amount of about 0.001 to about 5.0% by weight, orabout 0.001 to about 2.0% by weight. In another embodiment, the LAE ispresent in the oral composition in an amount of about 1.0 to about 2.0%by weight. In other embodiments, the LAE is present in amounts less than1% by weight, for example the LAE may be present in the oral compositionin an amount of from about 0.01 to about 1% by weight. In a preferredembodiment, the LAE is present in an amount from about 0.01 to 0.5% byweight. Most preferably, the LAE is present in the oral compositions inan amount sufficient to provide a synergistic weight ratio of the MBE tothe LAE in the composition. In particular, the LAE is preferably presentin the oral compositions in combination with MBE in an amount sufficientto result in a synergist reduction in the total salivary bacteria in theoral cavity of a consumer of the oral composition.

In various embodiments, the oral compositions will comprise from about 1to about 20 mg of LAE. In another aspect, the oral compositions willcomprise from about 1 to about 10 mg of LAE.

Oral Composition

The oral compositions of the present disclosure comprising MBE and LAEare in the form of a food-acceptable or food contact acceptable materialor carrier in which the MBE and LAE may be incorporated or dispersedwithout adverse effect. The oral composition may be a water-solublesolid or chewable solid such as chewing gums (e.g., tablet gums, pelletgums, stick gums, compressed gums, co-extruded layered gums, bubblegums, etc.), confections (e.g., mints, hard candies, chewy candies,chocolates, gels, confectionery pastes, etc.), or orally solubletablets, beads, or lozenges. In some embodiments, the composition is aconfectionery composition in the form of a coating, shell, film, syrup,or suspension. Such delivery systems are well known to one of skill inthe art, and preparation generally entails mixing the MBE and LAE into awarm base with flavor, non-cariogenic sweeteners and additionalorganoleptic components. In some embodiments, the oral composition maybe suitable for use by non-human mammals, and may be, for example, ananimal treat biscuit.

As discussed herein, the oral compositions of the present disclosurepreferably comprise a synergistic weight ratio of MBE to LAE. In certainembodiments, the weight ratio of MBE to LAE is preferably such that theoral composition provides a synergist reduction in the total salivarybacteria in the oral cavity of a consumer of the oral composition.Preferably, the oral composition comprises MBE and LAE in amountssufficient to reduce total salivary bacteria by at least 80%, morepreferably, by at least 90%, and more preferably, by at least 95%. Insuch embodiments, the weight ratios of MBE to LAE are preferably fromabout 2:1 to about 1:2, including from about 2:1 to about 1:1, or fromabout 1:1 to about 1:2, or from about 1:1 to about 1:1.25, or from about1:1.25 to about 1:1.

In certain embodiments, the synergistic reduction of the total salivarybacteria in the oral cavity may occur after chewing the oral compositionfor at least 10 minutes, including for at least 20 minutes.

One method of evaluating the efficacy of LAE and MBE against salivarybacteria is by determining the minimum inhibitory concentration (MIC).One suitable method for determining MIC is described in U.S. Pat. No.7,470,442, which is herein incorporated by reference. Briefly,chlorhexidine is used as a positive control and sterile water is used asa negative control. Methanol and Tween 80 are used as a solvent for MBE.Tween 80 is the common name for Polysorbate 80. Ninety-six-wellmicrotiter plates are used for this study. Each well contained 5×10⁵CFU/ml of bacteria, serially diluted agents and bacterial growth medium.All bacterial cultures are incubated at 37° C. and stationary. Bacterialgrowth is estimated spectrophotometrically at 660 nm, after 48 hours.The MIC for each test bacteria was defined as the minimum concentrationof test compound limiting turbidity to less than 0.05 absorbance at 660nm.

Another method for evaluating the efficacy of LAE and MBE againstsalivary bacteria is by determining the minimum bactericidalconcentration (MBC). One suitable method for determining MBC isdescribed in U.S. Pat. No. 7,470,442. Briefly, the MBC is determinedusing the 96-well microtiter plate serial dilutions as described abovefor the MIC test. Serial dilutions of cultures in wells showing novisible growth are performed and 10 microliters of culture are plated intriplicate on blood agar plates. Viable colonies are scored afterincubation of the plates for 48 hours at 37° C. For each test bacterium,the number of CFU/ml is determined in the initial inoculum. The MBC isdefined as the lowest concentration of a test compound that killed atleast 99.9% of the cells present in the initial inoculum.

Chewing Gums

In one embodiment, the oral composition of the present disclosure is achewing gum. The chewing gum may include the MBE and LAE in any of theamounts or weight ratios set forth herein. In certain embodiments, thechewing gum preferably comprises MBE and LAE in amounts such that thechewing gum provides a synergist reduction in the total salivarybacteria in the oral cavity of a consumer of the chewing gum. In theseembodiments, MBE and LAE are preferably present in the gum in a weightratio of from about 2:1 to about 1:2.

Chewing gum products of the present disclosure may be made using avariety of different compositions that are typically used in chewing gumcompositions. Suitable physical forms include sticks, tabs, chunks,solid balls, hollow balls, pellets, layers, and the like. Although exactingredients for each product form will vary from product to product, thespecific techniques will be known by one skilled in the art. In general,a chewing gum composition typically contains a water-insoluble chewablegum base portion, and a water-soluble bulk portion which includes watersoluble bulking agents (i.e., sugars, polyols) and other water solublecomponents and perhaps other active ingredients which may bewater-insoluble. The water-soluble portion dissipates with a portion ofthe flavor over a period of time during chewing. The gum base portion isretained in the mouth throughout the chew.

The chewing gum may comprise between approximately 5% to about 95% byweight gum base. Typically, the insoluble gum base may comprise betweenapproximately 10% and about 50% by weight of the gum, or fromapproximately 20% to about 40% by weight of the gum. The presentdisclosure contemplates employing any commercially acceptable gum base.

In general, the insoluble gum base may comprise elastomers, elastomersolvents, plasticizers, waxes, emulsifiers, and inorganic fillers.Plastic polymers, such as polyvinyl acetate, which behave somewhat asplasticizers, are also included. Other plastic polymers that may be usedinclude polyvinyl laurate, polyvinyl alcohol, and polyvinyl pyrrolidone.Gum base may comprise as low as 5% or as high as 95% by weight, or moretypically 20 to 40% by weight of the overall chewing gum composition.

Elastomers provide the rubbery texture which is characteristic ofchewing gum. Elastomers typically make up about 5 to about 25% by weightof the gum base. Synthetic elastomers may include, but are not limitedto, polyisobutylene, butyl rubber (isobutylene-isoprene copolymer),styrene copolymers (having for example a styrene-butadiene ratio ofabout 1:3 to about 3:1), polyisoprene, polyethylene, vinyl acetate-vinyllaurate copolymer, and combinations thereof.

Natural elastomers may include for example natural rubbers such as smokeor liquid latex and guayule, as well as natural gums such as chicle,jelutong, lechi caspi, perillo, sorva, massaranduba balata, massarandubachocolate, nispero, rosindinha, gutta hang kang and mixtures thereof.Preferred elastomers will depend on, for example, whether the chewinggum in which the base is used is adhesive or conventional, synthetic ornatural, bubble gum or regular gum. Elastomers provide the rubberytexture which is characteristic of chewing gum.

Elastomer solvents which are sometimes referred to as elastomerplasticizers, include but are not limited to natural rosin esters suchas glycerol esters, or partially hydrogenated rosin, glycerol esters ofpolymerized rosin, glycerol esters of partially dimerized rosin,glycerol esters of rosin, pentaerythritol esters of partiallyhydrogenated rosin, methyl and partially hydrogenated methyl esters ofrosin, pentaerthyritol esters of rosin, synthetics such as terpeneresins, polylimonene and other polyterpenes and/or any suitablecombination of the forgoing. Elastomer solvents are typically employedat levels of 5 to 30% by weight of the gum base.

Gum base plasticizers are sometimes referred to as softeners. Typically,these include fats and oils as well as waxes. Fats and oils aretypically vegetable oils which are usually partially or fullyhydrogenated to increase their melting point. Vegetable oils suitablefor such use include oils of cottonseed, soybean, palm (including palmkernal), coconut, shea, castor, peanut, corn, rapeseed, canola,sunflower, cocoa and others. Animal fats such as milk fat, tallow andlard may also be used. Commonly employed waxes include paraffin,microcrystalline and natural waxes such as beeswax and carnauba.Plasticizers are typically employed at a level of 5 to 40% by weight ofthe gum base.

Gum bases commonly contain optional additives such as antioxidants andcolors which serve their normal functions. Less commonly, flavors andsweeteners may be added to the gum base. These additives, if used, aretypically employed at levels of about 1% or less by weight of the gumbase.

The chewing gum and/or gum base may also include a filler component. Thefiller component is typically an inorganic powder such as calciumcarbonate, ground limestone, magnesium carbonate, talc, silicate typessuch as aluminum and magnesium silicate, dicalcium phosphate, tricalciumphosphate, cellulose polymers, such as wood, combinations thereof andthe like. The filler may constitute from 5% to about 50% by weight ofthe chewing gum.

Commonly used emulsifiers include mono- and diglycerides, such asglycerol monostearate, lecithin, glycerol triacetate, glycerolmonostearate, acetylated monoglycerides, fatty acids, and combinationsthereof. Emulsifiers are commonly used at a level of 1 to 10% by weightof the chewing gum.

The water-soluble portion of the chewing gum may comprise softeners,sweeteners, flavoring agents, and combinations thereof as well as otheroptional ingredients. For example, the majority of the water solubleportion of the chewing gum will typically comprise a water-soluble,powdered carbohydrate which serves as a bulking agent. In sugar gums,this most often is sucrose although other sugars such as fructose,erythrose, dextrose (glucose), levulose, tagatose, galactose, trehalose,corn syrup solids and the like, alone or in any combination may also beused.

Generally, sugarless chewing gums will employ sugar alcohols (alsocalled alditols, polyols or polyhydric alcohols) as bulking agents dueto their benefits of low cariogenicity, reduced caloric content andreduced glycemic values. Such sugar alcohols include sorbitol, mannitol,xylitol, hydrogenated isomaltulose, maltitol, erythritol, hydrogenatedstarch hydrolysate solids, and the like, alone or in any combination.Longer chain saccharides such as polydextrose andfructo-oligosaccharides are sometimes employed for their reduced caloricproperties and other health benefits. The bulking agents typicallycomprise approximately 5% to about 95% by weight of the gum composition.

Softeners, also known in the art as plasticizers or plasticizing agents,generally constitute between approximately 0.5% to about 15% by weightof the chewing gum. These include glycerin, propylene glycol and aqueoussweetener solutions (syrups). Examples of syrups include corn andglucose syrups which are usually prepared from hydrolyzed starch. Forsugarless products, the starch hydrolysate may be hydrogenated toproduce an ingredient known as hydrogenated starch hydrolysate syrups ormaltitol syrups.

In the case of sugarless gums, it is usually desirable to add highpotency sweeteners to compensate for the reduced sweetness resultingfrom substitution of sugar alcohols for the sucrose in sugar gums. Highpotency sweeteners may be defined as food acceptable compounds which areat least twenty times sweeter than sucrose. Commonly used high potencysweeteners include, but are not limited to, aspartame, sucralose,acesulfame-K, saccharin, thaumatin, alitame, neotame, and cyclamate, aswell as natural or plant-sourced sweeteners, such as perilla, stevia,monatin, monellin and chalcones.

Usage levels for high potency sweeteners may vary widely depending onthe potency of the sweetener, local market preferences, taste, and theregulatory environment. Typical levels can range from about 0.01% toabout 5% by weight, although some applications may dictate usage outsidethat range. These sweeteners may be combined together, or with non-highpotency sweeteners at varying levels to impart a desired sweetness tothe overall composition.

Flavors can be employed to impart a characteristic aroma and tastesensation to chewing gum products. These flavors may be natural orartificial (synthetic) in origin, or a combination of both. Although therange and combinations of flavors usable in chewing gums is nearlylimitless, they commonly include fruit flavors, such as lemon, orange,lime, grapefruit, tangerine, strawberry, apple, cherry, raspberry,blackberry, blueberry, banana, pineapple, cantaloupe, muskmelon,watermelon, grape, currant, mango, kiwi and many others as well ascombinations. Mint flavors include spearmint, peppermint, wintergreen,basil, corn mint, menthol and others and mixtures thereof. Spice flavorsinclude cinnamon, vanilla, clove, chocolate, nutmeg, coffee, licorice,eucalyptus, ginger, cardamom and many others. Also used are herbal andsavory flavors such as popcorn, chili, corn chip and the like. Flavorsare typically employed at levels of 0.1 to 10% by weight of the finishedgum product.

The chewing gum (along with any of the oral compositions) of the presentdisclosure may employ various sensates or organoleptic components.Generally, sensates may be any compounds that cause a cooling, heating,warming, salivating, tingling or numbing, for example, to the mouth orskin.

The organoleptic components are optionally selected from the groupconsisting of a flavoring agent, a cooling agent, a heating agent, amouthfeel agent, a tingling agent, a sweetening agent, a souring agent,a salivating agent, a bittering agent, a teeth whitening agent, ananti-cavity agent, a breath freshening agent, an audible agent, andcombinations thereof. These are well known in the art and are selectedbased on the desired profile of the gum or oral composition.

Cooling agents encompass any number of physiological cooling agents butdo not include traditional flavor-derivatives such as menthol ormenthone. Preferred cooling agents provide a cooling effect withoutimparting perceptible flavor of their own. Cooling agents are perceivedas cold or cool when contacted with the human body and, in particular,with the mucous membranes of the mouth, nose and throat. Cooling agentsmay be natural or synthetic chemicals used to impart a cooling sensationwith minimal aroma. Commonly employed cooling agents include ethylp-menthane carboxamide and other N-substituted p-menthane carboxamides,N,2,3-trimethyl-2-isopropyl-butanamide and other acyclic carboxamides,menthyl glutarate, 3-1-menthoxypropane-1,2-diol, isopulegol, menthylsuccinate, menthol propylene glycol carbonate, ethylene glycolcarbonate, menthyl lactate, menthyl glutarate, p-menthane-1,8-diol,menthol glyceryl ether, N-tertbutyl-p-menthane-3-carboxamide,p-menthane-3-carboxylic acid glycerol ester, methyl-2-isopryl-bicyclo(2.2.1), heptane-2-carboxamide, menthol methyl ether and others andcombinations thereof.

Trigeminal stimulants other than cooling agents may be employed in thechewing gums of the present disclosure. These include warming agentssuch as capsaicin, capsicum oleoresin, red pepper oleoresin, blackpepper oleoresin, piperine, ginger oleoresin, gingerol, shoagol,cinnamon oleoresin, cassia oleoresin, cinnamic aldehyde, eugenol, cyclicacetal of vanillin, menthol glycerin ether and unsaturated amides andtingling agents such as Jambu extract, vanillyl alkyl ethers such asvanillyl n-butyl ether, spilanthol, Echinacea extract and NorthernPrickly Ash extract.

Chewing gum generally conveys oral care benefits. In addition tomechanical cleaning of the teeth provided by the chewing action, salivastimulated by chewing, flavor and taste from the product conveysadditional beneficial properties in reducing bad breath, neutralizingacid, and the like.

The chewing gums of the present disclosure can provide these benefitsalong with the benefits disclosed herein, and may also be used asvehicles for the delivery of specialized oral care agents. For example,breath freshening agents include salts of zinc, salts of copper,polyphenols, mushroom extracts and mixtures thereof. Mouth odor maskingflavors such as cinnamon, mint, wintergreen, fruit flavors and mixturesthereof may also be used. Other dental actives, for example, toothwhiteners, fluoride, stain removers, calcium salts, phosphate salts andmixtures thereof, can also be used.

The chewing gums of the present disclosure may be used to deliverbiologically active agents to the chewer. Biologically active agentsinclude vitamins, minerals, anti-oxidants, nutritional supplements,dietary supplements, functional food ingredients (e.g., probiotics,prebiotics, lycopene, phytosterols, stanol/sterol esters, omega-3 fattyacids, adenosine, lutein, zeaxanthin, grape seed extract, Ginkgo biloba,and the like), OTC and prescription pharmaceuticals, vaccines, andnutritional supplements.

It may be desirable to take certain steps to increase or decrease therate of the release of the agents or other ingredients (e.g.,sweeteners, flavors) or to ensure that at least a minimum quantity isreleased. Such measures as encapsulation, isolation of the active, andmeasures to increase or decrease interactions of actives and ingredientsmay be employed to that end. These techniques are well known to oneskilled in the art.

In general by way of a non-limiting example, chewing gum is manufacturedby simultaneously or sequentially adding the various chewing gumingredients to a commercially available mixer known in the art. Afterthe ingredients have been thoroughly mixed, the gum mass is dischargedfrom the mixer and shaped into the desired form such as rolling sheetsand cutting into sticks, extruding into chunks or casting into pellets,which are then coated or panned.

The LAE and MBE may be incorporated simultaneously or sequentially intothe center portion of the gum and/or a gum coating. For instance, incertain embodiments, the LAE and MBE are combined and then incorporatedinto a center layer of the gum, or are center filled, using any suitabletechnique known in the art. In certain embodiments, the LAE and MBE arecombined and then incorporated in the coating of a gum using anysuitable technique known in the art, such as described herein.

In another embodiment, the LAE is incorporated into the center portionof the gum, and the MBE is incorporated into the gum coating. Forinstance, in certain embodiments, the LAE is incorporated into a centerlayer of the gum, or is center filled, using any suitable techniqueknown in the art, while the MBE is incorporated into a coating syrup orcoating flavor, such as described hereinafter.

In another embodiment, the MBE is incorporated into the center portionof the gum, and the LAE is incorporated into the gum coating. Forinstance, in certain embodiments, the MBE is incorporated into a centerlayer of the gum, or is center filled, using any suitable techniqueknown in the art, while the LAE is incorporated into a coating syrup orcoating flavor, such as described hereinafter.

Chewing gums of the present invention may also be coated. Pellet or ballgum is prepared as conventional chewing gum, but formed into pelletsthat are pillow shaped, or into balls. The pellets/balls can be thencoated or panned by conventional panning techniques to make a uniquecoated pellet gum.

Conventional panning procedures generally coat with sugars and otherpolyols, including, but not limited to, sucrose, dextrose, maltose,palatinose, xylitol, lactitol, maltitol, hydrogenated isomaltulose andother alditols or a combination thereof. These materials may be blendedwith panning modifiers including, but not limited to, gum arabic,maltodextrins, corn syrup, gelatin, cellulose type materials likecarboxymethyl cellulose or hydroxymethyl cellulose, starch and modifiedstarches, insoluble carbonates like calcium carbonate or magnesiumcarbonate and talc. Antitack agents may also be added as panningmodifiers which allow the use of a variety of carbohydrates and sugaralcohols to be used in the development of new panned or coated gumproducts. Flavors, sweeteners, and other organoleptic components mayalso be added with the coating with MBE and/or LAE to yield uniqueproduct characteristics.

The MBE and the LAE can be easily added to the coating syrup/solutionprepared for panning. In another embodiment, MBE and LAE can be used asa powder alone or blended with other components and used in conventionalpanning procedures. In some embodiments, the MBE and LAE eachindependently comprise from 0.001% to 5% by weight of the coating. Insome embodiments, the MBE and LAE are each independently of the otherpresent in the coating in an amount of about 0.001 to about 5.0% byweight, or about 0.001 to about 2.0% by weight. In another embodiment,the MBE and LAE are independently present in the coating in an amount ofabout 1.0 to about 2.0% by weight. In other preferred embodiments, theMBE and LAE are independently present in the coating in amounts lessthan 1% by weight, for example they may be present in the coating in anamount of from about 0.01 to about 1% by weight.

In some aspects of the present disclosure, the MBE and LAE are presentin the coating of an oral composition of the present disclosure in anamount such that the oral composition provides a synergist reduction inthe total salivary bacteria in the oral cavity of a consumer of the oralcomposition. For instance, the oral compositions of the presentdisclosure may comprise a synergistic weight ratio of MBE to LAE in thecoating, such that total salivary bacteria is reduced by at least 80%,and more preferably, by at least 90%, or by at least 95%, for instance,when the weight ratio of MBE to LAE in the coating is from about 2:1 toabout 1:2, including from about 2:1 to about 1:1, or from about 1:1 toabout 1:2. Alternatively, the weight ratio of MBE to LAE in the coatingis from about 1:1 to about 1:1.25 or from about 1:1.25 to about 1:1.

Candies/Confectioneries

As previously discussed, the oral compositions of the present disclosuremay alternatively be in the form of a confectionery product, includingfor example mints, hard candies, chewy candies, coated chewy candies,tableted candies, chocolates, nougats, confectionery pastes and thelike. These candies or confectionery products may comprise any of thevarious sugars and sweeteners, flavoring agents and/or colorants, aswell as other components, known in the art and/or set forth above in thediscussion of chewing gums. Additionally, these candies or confectioneryproducts may be prepared using processing conditions and techniquesknown in the art. The candies or confectionery products may include theMBE and LAE in any of the amounts set forth herein. In one particularembodiment, the candies or confectionery products may comprise up toabout 1.0% by weight of MBE and about 2.0% by weight of LAE.

Preferably, the candy or confectionery product will comprise MBE and LAEin amounts such that the candies or confectionery products provide asynergist reduction in the total salivary bacteria in the oral cavity ofa consumer of the product. In such embodiments, the MBE and LAE arepreferably present in a weight ratio of from about 2:1 to about 1:2, andmore preferably, in a weight ratio of from about 1:1 to about 1:1.25.

By way of a non-limiting example, a hard candy can be primarilycomprised of corn syrup and sugar, and derives its name from the factthat it contains only between 1.0% and 4% by weight moisture. Inappearance, these types of candies are solid, but they are actuallysupercooled liquids, which are far below their melting points. There aredifferent types of hard candies. Glass types are usually clear or madeopaque with dyes; and grained types, which are always opaque, due toentrapped air and/or moisture.

For illustrative purposes, it is to be noted that a continuous makingprocess for making deposited glass types, with a sugar base can begenerally made as follows. Sugar corn syrup mixture is spread over acylinder heated by high pressure steam. Rapid head exchange causes thewater in the syrup to evaporate. The cooked syrup is discharged, colorsand flavors are added. These can be conveyed directly to hoppers whichthen discharge directly into molds. The candy is conveyed to batchrollers, which shapes and sizes the batch. The candy enters a former,which shapes the individual pieces into discs, balls, barrels, etc. Thepresent disclosure can be made into any shape, circles, squares,triangles etc., also into animal shapes or any other novelty moldingavailable. The candy is then cooled, wrapped and packaged.

For grained types of candy, water and sugar are the basic componentsbeing mixed with other ingredients, and cooked at high temperatures(290° F. to 310° F.), causing the water to turn to steam. The product istransferred to a cooling wheel, where it is collected in about 150 poundbatches, placed in a pulling machine to aerate the product, and theflavor is added. The candy is transferred to batch rollers where it isshaped and sized. The candy then enters a former, which shapes theindividual pieces. The candy is cooled at a relative humidity of 35% andenters a rotating drum where it is coated with a fine sugar. The candyis then conveyed to the graining room for four hours at 90° F. and 60%humidity. The entrapped air and moisture causes the product to grain.The MBE and LAE may be added at any suitable point during themanufacturing process, and typically during addition of the flavors.

Lozenges, Beads, and Tablets

In some embodiments, the oral composition may be a lozenge, bead, ortablet. The lozenge, bead, or tablet may include the MBE and LAE in anyof the amounts set forth herein. In one embodiment, the lozenge, bead,or tablet may comprise up to about 1.0% by weight of MBE and about 2.0%by weight of LAE.

In one particular embodiment, the lozenge, bead, or tablet will compriseMBE and LAE in amounts such that the lozenge, bead, or tablet provides asynergist reduction in the total salivary bacteria in the oral cavity ofa consumer. In such embodiments, the lozenge, bead, or tablet willpreferably comprise a synergistic weight ratio of MBE to LAE sufficientto reduce salivary bacteria by at least 80%, more preferably, by atleast 90%, or by at least 95% when the weight ratio is from about 2:1 toabout 1:2, including from about 2:1 to about 1:1, and from about 1:1 toabout 1:2.

The orally acceptable vehicle or carrier used to form a lozenge, bead,or tablet is typically a non-cariogenic, solid water-soluble polyhydricalcohol (polyol) such as, but not limited to, mannitol, xylitol,sorbitol, maltitol, erythritol, hydrogenated starch hydrozylate (HSH),hydrogenated glucose, hydrogenated disaccharides or hydrogenatedpolysaccharides, in an amount of about 85 to about 95% by weight of thetotal composition. Emulsifiers such as glycerin, and tabletinglubricants, in minor amounts of about 0.1 to 5% by weight, may beincorporated into the tablet, bead or lozenge formulation to facilitatethe preparation of the tablet beads and lozenges. Suitable lubricantsinclude vegetable oils such as, but not limited to, coconut oil,magnesium stearate, aluminum stearate, talc, starch and polyethyleneglycols. Suitable noncariogenic gums include kappa carrageenan,carboxymethyl cellulose, hydroxyethyl cellulose and the like.

A lozenge, bead, or tablet may optionally be coated with a coatingmaterial such as waxes, shellac, carboxymethyl cellulose,polyethylene/maleic anhydride copolymer or kappa-carrageenan to furtherincrease the time it takes the tablet or lozenge to dissolve in themouth. The uncoated tablet or lozenge is slow dissolving, providing asustained release rate of active ingredients of about 3 to 5 minutes.Accordingly, the solid dose tablet, bead, and lozenge, compositions ofthis embodiment affords a relatively longer time period of contact inthe oral cavity with the MBE and LAE of the present invention.

In some embodiments, the oral composition is a lozenge. The lozenge maycomprise a core in the form of a liquid, powder, syrup, suspension,fondant, toffee, or chocolate comprising the LAE, and a coating, such asdescribed herein, comprising the MBE. In another embodiment, the lozengemay comprise a core comprising the MBE, and a coating, such as describedherein, comprising the LAE.

In another embodiment, the MBE and LAE are both incorporated into thecoating of the lozenge. Suitable amounts of MBE and LAE for inclusion inthe coating include those set forth above for chewing gum coatings. Instill another embodiment, the MBE and LAE are both incorporated into thecore of the lozenge. Method for preparing these embodiments are wellknown in the art.

Animal Products

In some embodiments, the oral composition may be suitable for use bynon-human mammals, and may be, for example, an animal treat (e.g., abiscuit).

Food products and supplements for animals are well known in the art andare preferably made with any suitable dough. Food supplement doughgenerally comprises at least one of flour, meal, fat, water, andoptionally particulate proteinaceous particles (for texturization) andflavor. For instance, when the desired product is a biscuit,conventional dough can be used, optionally containing discrete particlesof meat and/or meat by-products or farinaceous material. Examples ofsuitable dough for the production of hard and soft (including humectantfor water control) animal biscuits are disclosed in U.S. Pat. Nos.5,405,836; 5,000,943; 4,454,163; 4,454,164, the contents of each ofwhich are incorporated herein by reference. Such compositions arepreferably baked. The MBE and LAE may be added with the flavor, includedin an interior reservoir with a soft center, or coated onto the surfaceof a baked food supplement by dipping or spraying. Preferably, theanimal product will comprise MBE and LAE in amounts such that the animalproduct provides a synergist reduction in the total salivary bacteria inthe oral cavity. In one embodiment, the MBE and LAE are present in aweight ratio of from about 2:1 to about 1:2, and preferably from about1:1 to about 1:1.25. Any other suitable means known to one of skill inthe art for delivering active ingredients to animals may also be used.

Method of Preparation

In addition to the above-noted advantages to oral compositionscomprising MBE and LAE, it has also surprisingly been discovered thatinclusion of LAE in an oral composition in combination with MBE improvesthe loading efficiency of MBE and release rate of the MBE from the oralcomposition, as compared to oral compositions comprising MBE alone. Thiseffect is further enhanced when the MBE and LAE are pretreated prior toincorporating them into the oral composition. In particular, it isbelieved that the loading efficiency and release rate of MBE fromchewing gum can be increased by at least 20%, and typically by at least33% when MBE and LAE are pretreated prior to incorporation into the oralcomposition. In particular, in certain embodiments, pretreating bysieving and/or sonicating, results in a loading efficiency of at least80%, and preferably, at least 90% in conventional chewing gums.

In certain embodiments, at least 60%, and preferably, at least 80% ofthe MBE present in the oral composition is released into the oral cavityof a consumer after chewing the oral composition for at least 10minutes, or at least 20 minutes. In certain embodiments, at least 60%and preferably, at least 90% of the LAE present in the oral compositionis released into the oral cavity of a consumer after chewing the oralcomposition for at least 10 minutes, or at least 20 minutes.

Thus, in one particular preferred embodiment, the present disclosure isdirected to a method of making a coated oral composition. The methodcomprises pretreating MBE and LAE to form a preblend mixture, adding thepreblend mixture to a coating syrup, and applying the coating syrup toan oral composition to produce the coated oral composition. The MBE andLAE may be pretreated by sieving the MBE and LAE prior to addition tothe coating syrup; sonicating the MBE and LAE prior to addition to thecoating syrup; blending the MBE and LAE with one or more organolepticcomponents prior to addition to the coating syrup; pre-dissolving theMBE and LAE in a flavoring agent, glycerol, and/or medium-chaintriglyceride (MCT) oil; or combinations thereof.

In still other embodiments, the present disclosure is directed to amethod of making a chewing gum composition. The method comprisespretreating MBE and LAE to form a preblend mixture, and forming thechewing gum composition from the preblend mixture. The MBE and LAE maybe pretreated by sieving the MBE and LAE; sonicating the MBE and LAE;blending the MBE and LAE with a powdered gum base; pre-dissolving theMBE and LAE in a flavoring agent, glycerol, and/or medium-chaintriglyceride (MCT) oil; or combinations thereof.

In certain embodiments, the amount of MBE and LAE included in thepreblend mixture is sufficient to provide a synergist reduction in thetotal salivary bacteria in the oral cavity of a consumer of the oralcomposition. In particular, embodiments, the MBE and LAE are added tothe preblend mixture in a weight ratio of from about 2:1 to about 1:2,including from about 1:1 to about 1:2, or from about 2:1 to about 1:1.

In some embodiments, the MBE and LAE are pretreated by blending the MBEand LAE with one or more organoleptic components prior to addition tothe oral composition. In particular embodiments, the preblend mixture isadded to a coating syrup and applied to the oral composition. Suitableorganoleptic components include, but are not limited to, a flavoringagent, a cooling agent, a heating agent, a mouthfeel agent, a tinglingagent, a sweetening agent, a souring agent, a salivating agent, abittering agent, a teeth whitening agent, an anti-cavity agent, a breathfreshening agent, an audible agent, and combinations thereof. In stillother embodiments, the MBE and LAE are pretreated by blending the MBEand LAE with a powdered gum base prior to addition to a gum composition(e.g., a compressed chewing gum composition). In still otherembodiments, the MBE and LAE are pretreated by pre-dissolving the MBEand LAE in a flavoring agent, glycerol, and/or medium-chain triglyceride(MCT) oil prior to addition to a gum composition.

In some embodiments, the MBE and LAE are combined and sieved, sonicatedor both prior to blending with the one or more organoleptic components,or the powdered gum base. In another embodiment, the MBE and LAE areblended with the organoleptic components or the powdered gum base, andthe resulting mixture sieved, sonicated or both. Preferably, a mixtureof MBE and LAE is sieved then sonicated prior to blending with theorganoleptic components or the powdered gum base.

Any of the oral compositions disclosed herein may be prepared using themethods described herein. In particular embodiments, the oralcomposition prepared according to the method of the disclosure isselected from the group consisting of chewing gums, confections, mints,tablets, beads, and lozenges. Preferably, the oral composition is achewing gum or a mint. More preferably, the oral composition is achewing gum, such as a coated chewing gum, a center-filled chewing gum,or a coated center-filled chewing gum. Preferably, the gum is a coatedchewing gum.

Methods of Use

As discussed herein, it has surprisingly been discovered that MBE incombination with LAE is synergistically effective at reducing totalsalivary bacteria. This combination thus greatly improves and facilitiesthe reduction of salivary bacteria in the oral cavity of a consumer.Incorporating the combination of an effective amount of MBE and LAE intoan oral composition can thus provide an oral composition that reducestotal salivary bacteria in the oral cavity of a consumer of the oralcomposition. The oral compositions of the present disclosure may also beeffective for use in inhibiting the formation of plaque biofilm, in theremoval of existing plaque, and in reducing halitosis associated withcertain salivary bacteria.

Thus, in another aspect, the present disclosure is directed to a methodfor reducing total salivary bacteria in an oral cavity of a mammaliansubject. The method comprises contacting a composition of the presentdisclosure with the oral cavity of said subject. The mammalian subjectmay be human or a non-human animal. The composition may be contactedwith the oral cavity for at least 10 minutes, or at least about 20minutes.

The invention is illustrated by, but not limited to, the followingExamples.

EXAMPLES Example 1: Synergistic Anti-Microbial Effect of MBE and LAE

In this example, the anti-microbial effect of MBE and LAE againstsalivary bacteria was examined. The Minimum Inhibitory Concentration(MIC) and Minimum Bactericidal Concentration (MBC) for MBE and LAEagainst four salivary bacteria and whole saliva was determined.

Preparation of Bacterial Strains

S. mutans (ATCC No. 25715), S. sobrinus (ATCC 33478), S. salivarius(ATCC 13419) and F. nucleatum (ATCC No. 10953) were purchased fromAmerican Type Culture Center (ATCC, MD). S. mutans, S. sobrinus, and S.salivarius were incubated for 24 hours in Schaedler broth containing 1ppm vitamin K and 10 ppm hemin. F. nucleatum was incubated anaerobicallyfor 48 hrs.

For testing total salivary bacteria (whole saliva), 30 ml of saliva wascollected from a minimum of 3 healthy human volunteers by chewing astandard gum base. The freshly collected saliva was vortexed briefly anddirectly added to nutrient broth.

Magnolia Bark Extract Preparation

A 1% (w/v) solution of MBE powder (95% magnolol, 5% honokiol, HonseaSunshine Biotech Co., Ltd., Guangzhou, China) in 100% ethanol wasprepared, and used in the current example.

LAE Preparation

LAE-CF (containing 99% pure LAE) was obtained from Vedeqsa of Barcelona,Spain, and used in the current example.

Minimum Inhibitory Concentration (MIC)

The MIC of LAE and MBE against the four oral bacteria described suprawas determined. The effectiveness of MBE and LAE on total salivarybacteria was evaluated using whole saliva.

Chlorhexidine was used as a positive control and sterile water was usedas a negative control. MBE was dissolved in ethanol to produce a workingsolution containing 1% of MBE. It was added to Shaedler broth thatcontained 10 ppm of Hemin, 1 ppm of Vitamin K and a minimum of 1×10⁶CFU/ml of bacterial strains. The solution was serially diluted two-foldso that each subsequent dilution contained 50% of compounds of theprevious dilution while maintaining a constant level of nutrients foreach dilution.

All bacterial cultures were incubated at 37° C. and stationary.Bacterial growth was estimated spectrophotometrically at 660 nm, after48 hours. The MIC for each test bacteria was defined as the minimumconcentration of test compound limiting turbidity to less than 0.05absorbance at 660 nm.

Minimum Bactericidal Concentration (MBE)

The MBC of MBE and LAE against the four oral bacteria described suprawas determined using the MBC protocol set forth below. The effectivenessof MBE on total salivary bacteria was evaluated using whole saliva.

The MBC was determined by serial dilutions as described above for theMIC test. Serial dilutions of cultures in test tubes that showed novisible growth were performed and 50 microliters of culture were platedin triplicate on blood agar plates. Viable colonies were scored afterincubation of the plates for 48 hours at 37° C. For each test bacterium,the number of CFU/ml was determined in the initial inoculum. The MBC wasdefined as the lowest concentration of a test compound that killed atleast 99.9% of the cells present in the initial inoculum.

Results

Tables 1 and 2 below display the MIC and MBC values for MBE and LAEagainst select oral bacteria.

TABLE 1 MIC of LAE and MBE against oral bacteria (in ppm) S. S. S. F.Whole Sample mutans salivarius sobrinus nucleatum Saliva LAE-CF 6.3 6.36.3 12.5 50 MBE 25 25 25 12.5 25

TABLE 2 MBC of LAE and MBE against oral bacteria (ppm) S. S. S. F. WholeSample mutans salivarius sobrinus nucleatum Saliva LAE-CF 12.5 12.5 12.512.5 — MBE 25 25 50 12.5 25

As can be seen from Table 1, LAE-CF had an excellent MIC against S.mutans, S. salivarious and S. sobrinus, as well as the whole salivarybacteria.

In order to determine whether MBE and LAE demonstrate a synergisticeffect against oral bacteria, the Fractional Inhibitory Concentration(FIC) Index was calculated. Calculation of the FIC is disclosed in U.S.Pat. No. 7,074,447, which is herein incorporated by reference. Briefly,the FIC Index is calculated according to the following formula:FIC=[Q _(A) /Q _(a) +Q _(B) /Q _(b)] where

Q_(A)=the MIC of component A combined with component B.

Q_(a)=the MIC of component A alone.

Q_(B)=the MIC of component B combined with component A.

Q_(b)=the MIC of component B alone.

If the FIC<1, components A and B are synergistic; if 1≤FIC≤2, componentsA and B are additive; and if 2<FIC, components A and B are antagonistic.The lower the FIC value (when FIC<1), the stronger the synergisticeffect between the two components.

The FIC for three MBE and LAE mixtures against total salivary bacteria(whole saliva) are set forth in Table 3.

TABLE 3 Synergistic effect of LAE and MBE on total salivary bacteriaLAE-CF/ LAE-CF/ LAE-CF/ Sample LAE-CF MBE MBE 2:1 MBE 1:1 MBE 1:2 MIC(ppm) 50 25 12.5/6.25 12.5/12.5 6.25/12.5 FIC 1 1 0.50 0.75 0.625

As can be seen from Table 3, LAE and MBE have a strong synergisticgerm-kill effect against total salivary bacteria. For example, thecombination of MBE and LAE (1:2 ratio) show an FIC of 0.50, which is2-fold more potent than MBE or LAE used alone.

Example 2: Loading Efficiency and Release of LAE from Gum

In this example, the loading efficiency and release of LAE from gum wasevaluated.

For evaluating release of LAE from pellet gum, samples were formulatedwith LAE-CF in peppermint gum. Samples were chewed for 20 minutes byvolunteers. The bolus of the gum was stored and frozen until analysis.The gum bolus from 6 chewers and unchewed LAE gum was tested via HPLCand compared to determine chew-out/release from gum. Table 4 shows therecovery and release of LAE from the gum center.

TABLE 4 Loading Efficiency of LAE from Peppermint Flavored Gum CenterHPLC Release of Formulation analytical Loading LAE after input of resultof efficiency 20 min Sample LAE LAE of LAE of chew Peppermint stick0.20% 0.169%  85% 25.4% with 0.2% LAE Peppermint pellet 0.075% 0.076%100%  17% with 0.075% LAE

As can be seen from Table 4, about 85%˜100% of the LAE that was addedduring formulation was present in the gum samples, indicating that onlyabout 0˜15% of the LAE added during formulation was lost duringformulation. Of the LAE present in the gum samples, 25.4% of the LAE wasreleased from a stick gum, and 17% of the LAE was released from a pelletgum after 20 minutes of chew.

Example 3: Loading Efficiency and Release of MBE and LAE from Gum

The following gum formulations were used to evaluate the loadingefficiency and release of MBE or MBE plus LAE from gum.

ID Composition Loading 1 Placebo gum Wintergreen flavor (no MBE or LAE)2 MBE 1.2% by wt. in coating 12 mg/serving 3 MBE 1.2% by wt. in coating12 mg/serving consumed as suck-chew 4 MBE 1.2% by wt. in coating MBE: 12mg/serving, and LAE 1.5% by wt. in coating LAE: 15 mg/serving

For composition 3 (MBE-suck), the gum pellet was consumed by sucking thepellet for 2 minutes to completely dissolve the coating layer, followedby chewing for 8 minutes. Compositions 1, 2, and 4, were consumed byregular chewing for 10 minutes. The amount of MBE and LAE before (load)and after (release) chewing was determined. The results are set forth inTable 5.

TABLE 5 Loading and Delivery Results (in mg) Name ID MBE load MBErelease LAE load LAE release Ctrl 1 0.00 0.01 MBE 2 7.56 5.32 MBE + LAE3 10.41 7.71 11.70 9.00 MBE-suck 4 10.32 9.61

As can be seen from Table 5, release of MBE and LAE is higher whenformulated in the coating of a chewing gum. In addition, the suck-chewmethod further improves the release of MBE.

Example 4: Coated Chewing Gum

In this example, coating compositions containing MBE or MBE and LAE areprepared. The coating compositions can be used to prepare coated oralcompositions containing MBE and LAE.

A coating composition is prepared according to the formula set forth inTable 6.

TABLE 6 Coating composition Ingredient Weight % Polyol 63.83 Water 22.2240% gum tahla 12.39 Color 0.42 High potency 0.42 sweetener Cooling agent0.72 Total 100.00

MBE coating composition: 3.75 g of MBE is added to 300 g of the coatingcomposition in Table 6. The resulting coating composition comprises1.25% by weight of MBE. The MBE coating composition may be applied tooral compositions, such as chewing gum, in an amount sufficient toprovide a concentration of MBE of 12 mg/serving.

MBE/LAE coating composition: 3.75 g of MBE and 4.65 g of LAE are addedto 300 g of the coating composition in Table 6. The resulting coatingcomposition comprises 1.25% by weight of MBE and 1.55% by weight of LAE.The MBE/LAE coating composition may be applied to oral compositions,such as chewing gum, in an amount sufficient to provide a concentrationof MBE of 12 mg/serving and a concentration of LAE of 15 mg/serving.

Example 5: Effect of Chewing Gum Comprising MBE and LAE on AcidProduction and Regrowth of Human Supragingival Plaque Bacteria

In this example, the effect of MBE and LAE on the regrowth andglycolysis of human supragingival plaque, and the effectiveness ofchewing gum as a delivery mechanism, was evaluated using the PlaqueGlycolysis and Regrowth Method (PGRM).

Six adults ages 18-65 years old (five females, one male) of all race andgender participated in the study. Participants refrained from oralhygiene the night before and the morning of the test visit. Theirovernight supragingival plaque was collected (upper and lower left)before chewing a gum sample (pre-treatment sample, “pre”). Participantsthen chewed one of the gum samples for 10 min, and their upper and lowerright plaque samples were collected 20 min after chewing (post-treatmentsamples, “post”). All plaque samples before and after chewing weretested in vitro for their ability to grow and produce acid using thePGRM, as described in White et al., J. Clin. Dent. 6 [special issue]:59-70, 1995, which is herein incorporated by reference. Their ability toform in vitro biofilm was also tested.

Treatment Groups

The gum samples evaluated in this test were: a) a gum base control; b)an experimental gum comprising both MBE and LAE (“MBE gum”); and c) agum without MBE or LAE (“control gum”). The MBE gum (3000 mg servingsize, administered as two 1500 mg pellets) was identical to the controlgum, except comprised 15 g (0.5 wt %) of MBE and 2 g (0.067 wt. %) ofLAE per serving.

PGRM—Glycolysis Activity Measurements

The in vivo treated plaque samples (“post”) were compared to theuntreated plaque samples (“pre”) for glycolytic activity. The pre- andpost-treatment plaque samples were dispersed in buffer, and the opticaldensity (OD) of the samples (measured at 600 nm) was adjusted to0.20±0.01 with addition of 0.03% buffer (tryptic soy broth, “TSB”)solution to obtain normalized biomass plaques. One mL of the normalizedbiomass plaques was pipetted into a 2 mL Eppendorf vial, and bacterialmetabolism was initiated by the addition of 50 μL of a 40% sucrose stocksolution. The normalized plaques were subsequently incubated at 37° C.and 120 rpm agitation. Acid production following 2 and 4 hours ofincubation was measured by pH change in the suspension buffer. Theresults are set forth in Tables 7-9, and in FIGS. 1 and 2.

TABLE 7 Effect of Chewing MBE Gum (MBE and LAE) on Acid Production ofHuman Supragingival Plaque Bacteria pH data ΔpH Pre Post Pre Post 0 2 hr4 hr 0 2 hr 4 hr 2-0 hr 4-0 hr 4-2 hr 2-0 hr 4-0 hr 4-2 hr 1 6.63 4.974.49 6.85 6.18 4.84 −1.66 −2.14 −0.49 −0.67 −2.01 −1.35 2 7.08 5.46 4.867.07 5.57 4.88 −1.63 −2.22 −0.60 −1.50 −2.19 −0.69 3 7.26 4.99 4.52 7.305.18 4.64 −2.26 −2.74 −0.47 −2.12 −2.66 −0.54 4 6.77 4.75 4.34 6.83 4.984.43 −2.02 −2.43 −0.41 −1.85 −2.40 −0.55 5 6.58 4.93 4.64 6.71 4.93 4.63−1.65 −1.94 −0.29 −1.79 −2.09 −0.30 6 6.92 4.91 4.64 7.14 4.98 4.65−2.01 −2.28 −0.27 −2.17 −2.49 −0.33 avg 6.87 5.00 4.58 6.98 5.30 4.68−1.87 −2.29 −0.42 −1.68 −2.31 −0.62

TABLE 8 Effect of Chewing Control Gum (No MBE/LAE) on Acid Production ofHuman Supragingival Plaque Bacteria pH data ΔpH Pre Post Pre Post 0 2 hr4 hr 0 2 hr 4 hr 2-0 hr 4-0 hr 4-2 hr 2-0 hr 4-0 hr 4-2 hr 1 6.48 5.414.85 7.09 6.24 5.24 −1.07 −1.63 −0.56 −0.85 −1.85 −1.00 2 6.68 4.96 4.626.03 4.94 4.54 −1.72 −2.06 −0.34 −1.09 −1.49 −0.40 3 7.22 4.65 4.21 7.434.76 4.27 −2.57 −3.01 −0.44 −2.67 −3.16 −0.49 4 6.80 5.68 4.62 6.84 5.474.59 −1.13 −2.19 −1.06 −1.37 −2.25 −0.88 5 6.79 4.87 4.66 6.80 4.99 4.74−1.92 −2.13 −0.22 −1.82 −2.06 −0.24 6 6.27 4.98 4.64 6.34 4.92 4.61−1.29 −1.63 −0.34 −1.42 −1.73 −0.31 avg 6.71 5.09 4.60 6.75 5.22 4.66−1.62 −2.11 −0.49 −1.54 −2.09 −0.55

TABLE 9 Effect of Chewing Non-Flavored Gum Base on Acid Production ofHuman Supragingival Plaque Bacteria pH data ΔpH Pre Post Pre Post 0 2 hr4 hr 0 2 hr 4 hr 2-0 hr 4-0 hr 4-2 hr 2-0 hr 4-0 hr 4-2 hr 1 6.76 5.084.48 6.81 5.47 4.72 −1.68 −2.28 −0.60 −1.34 −2.09 −0.75 2 7.22 5.28 4.687.12 5.46 4.77 −1.95 −2.55 −0.60 −1.66 −2.35 −0.69 3 6.99 5.18 4.58 6.965.46 4.74 −1.81 −2.41 −0.60 −1.50 −2.22 −0.72 4 6.51 5.59 4.84 6.62 5.464.79 −0.92 −1.67 −0.75 −1.16 −1.83 −0.67 5 6.76 5.48 4.66 6.75 5.14 4.50−1.28 −2.10 −0.82 −1.61 −2.25 −0.64 6 6.64 5.54 4.75 6.69 5.30 4.65−1.10 −1.89 −0.79 −1.39 −2.04 −0.66 avg 6.81 5.36 4.66 6.82 5.38 4.69−1.46 −2.15 −0.69 −1.44 −2.13 −0.69

Inhibiting the ability of plaque bacteria to metabolize sugar to acidsis one measure of the effectiveness of antimicrobial agents, with areduction in acid production following treatment being evidence of anantimicrobial effect. As can be seen from the results set forth inTables 7-9 and FIGS. 1 and 2, the pH for the MBE gum (containing MBE andLAE) treated plaque sample was 0.3 pH units higher after two hours, ascompared to the untreated (“pre”) control plaque sample, indicating areduced acid-forming activity of the bacteria exposed to this gum. Theresults thus show a positive trend in reducing acid production up to 2hours after chewing of the MBE gum for 10 minutes. No statisticallysignificant trend in reduction of acid production was seen with the gumbase and control gum.

PGRM—Plaque Regrowth Activity

The effects of MBE and LAE on plaque growth were determined by assessingthe bacterial regrowth of normalized plaque samples in aerobic media. A300 aliquot of the dispersed plaque from the glycolysis vials preparedabove was transferred to a separate 2 mL Eppendorf vial containing 0.5mL of 6% (w/w) BBL TSB (pH 7.1±0.2) along with 100 μL of sterile water.Bacterial growth in the broth was accelerated by the addition of 50 μLof stock 40% sucrose solution. Following sample preparation, the initialoptical density of the plaque dispersion was measured at 600 nm in a 3mL disposable curvette in a spectrometer. Samples were incubated in 2 mLEppendorf tubes at 37° C. at 1200 rpm. Plaque samples were incubated for4 hours, and measured for optical density (600 nm) at 2 and 4 hoursfollowing homogenization with a pellet mixer. The results are set forthin Tables 10-13 and FIGS. 3 and 4. Regrowth results are reported as thefinal plaque dispersion turbidity (OD₆₀₀).

TABLE 10 Effect of Chewing MBE Gum (MBE and LAE) on Regrowth (OD₆₀₀) ofHuman Supragingival Plaque Bacteria Pre Post Subject 0 hr 2 hr 4 hr 0 hr2 hr 4 hr #1 0.033 0.059 0.262 0.030 0.040 0.100 #2 0.057 0.084 0.4500.055 0.064 0.376 #3 0.052 0.100 0.623 0.054 0.080 0.407 #4 0.047 0.0850.530 0.044 0.069 0.439 #5 0.066 0.169 0.640 0.064 0.166 0.705 #6 0.0670.113 0.421 0.075 0.088 0.279 avg 0.054 0.102 0.488 0.054 0.084 0.384

TABLE 11 Effect of Chewing Control Gum on Regrowth (OD₆₀₀) of HumanSupragingival Plaque Bacteria Pre Post Subject 0 hr 2 hr 4 hr 0 hr 2 hr4 hr #1 0.029 0.052 0.162 0.021 0.025 0.067 #2 0.057 0.130 0.762 0.0570.134 0.712 #3 0.056 0.100 0.952 0.056 0.095 0.895 #4 0.032 0.041 0.3410.025 0.036 0.261 #5 0.064 0.151 0.798 0.063 0.149 0.763 #6 0.044 0.0740.408 0.053 0.052 0.403 avg 0.047 0.091 0.570 0.046 0.082 0.517

TABLE 12 Effect of Chewing Non-Flavored Gum Base on Regrowth (OD₆₀₀) ofHuman Supragingival Plaque Bacteria Pre Post Subject 0 hr 2 hr 4 hr 0 hr2 hr 4 hr #1 0.039 0.095 0.313 0.030 0.051 0.182 #2 0.066 0.104 0.8390.061 0.093 0.634 #3 0.065 0.133 0.730 0.065 0.138 0.708 #4 0.033 0.0330.221 0.035 0.051 0.321 #5 0.060 0.065 0.301 0.063 0.087 0.406 #6 0.0640.092 0.420 0.058 0.078 0.442 avg 0.054 0.087 0.471 0.052 0.083 0.449

TABLE 13 Regrowth Ratios (OD_(final)/OD_(initial)) MBE Gum Control GumGum Base 2 hr 4 hr 2 hr 4 hr 2 hr 4 hr subject pre post Pre post prepost Pre post pre post Pre post #1 1.79 1.36 7.92 3.39 1.79 1.19 5.593.19 2.44 1.70 8.03 6.07 #2 1.45 1.17 7.65 6.83 2.28 2.37 13.35 12.601.58 1.52 12.80 10.40 #3 1.92 1.50 11.83 7.60 1.80 1.70 17.14 15.99 2.052.11 11.22 10.90 #4 1.91 1.59 11.88 9.50 1.23 1.29 9.97 9.26 1.00 1.466.70 9.17 #5 2.55 2.54 9.72 10.85 2.37 2.36 12.56 12.09 1.08 1.38 5.026.44 #6 1.69 1.17 6.28 3.72 1.68 0.98 9.27 7.60 1.43 1.36 6.67 7.68 avg1.89 1.55 9.22 6.98 1.86 1.65 11.31 10.12 1.60 1.59 8.41 8.44 SD* 0.370.51 2.32 3.01 0.42 0.60 3.96 4.46 0.56 0.29 2.99 2.03 *Standarddeviation

As can be seen from these results, there was a positive trend inreducing short-term plaque bacteria regrowth of up to 4 hours afterchewing the MBE gum (containing MBE and LAE) for 10 minutes, while thecontrol gum and gum base did not inhibit plaque bacteria regrowth. Theseresults suggest that chewing gum may serve as an effective oral deliverysystem of antimicrobial agents for short-term plaque control.

This written description uses examples to disclose the invention,including the best mode, and also to enable any person skilled in theart to practice the invention, including making and using any devices orsystems and performing any incorporated methods. The patentable scope ofthe invention is defined by the claims, and may include other examplesthat occur to those skilled in the art. Such other examples are intendedto be within the scope of the claims if they have structural elementsthat do not differ from the literal language of the claims, or if theyinclude equivalent structural elements with insubstantial differencesfrom the literal languages of the claims.

What is claimed is:
 1. An oral composition for reducing total salivary bacteria in an oral cavity of a consumer, the composition comprising magnolia bark extract (MBE) and L-arginine, N^(α)-lauroyl-ethyl ester (LAE), wherein the oral composition comprises the MBE and LAE in amounts that provide a synergistic reduction of the total salivary bacteria in the oral cavity.
 2. The oral composition of claim 1, wherein the weight ratio of MBE to LAE is from about 2:1 to about 1:2.
 3. The oral composition of claim 1, wherein the oral composition comprises from about 1 to about 20 mg of MBE.
 4. The oral composition of claim 1, wherein the oral composition comprises from about 1 to about 20 mg of LAE.
 5. The oral composition of claim 1, wherein the total salivary bacteria in the oral cavity is reduced by at least 80%.
 6. The oral composition of claim 1, wherein the oral composition is selected from the group consisting of a chewing gum, a confection, a mint, a tablet, a bead, and a lozenge.
 7. The oral composition of claim 1, wherein the oral composition is a chewing gum, and the synergistic reduction of total salivary bacteria in the oral cavity occurs after a chewing time of at least 10 minutes.
 8. A coated oral composition for reducing total salivary bacteria in an oral cavity of a consumer, the coated oral composition comprising MBE and LAE in a weight ratio from about 2:1 to about 1:2 that provide a synergistic reduction of the total salivary bacteria in the oral cavity.
 9. The coated oral composition of claim 8, wherein the total salivary bacteria in the oral cavity is reduced by at least 90%.
 10. The coated oral composition of claim 8, wherein the MBE comprises from about 1% to about 2% by weight of the coating.
 11. The coated oral composition of claim 8, wherein the LAE comprises from about 1% to about 2% by weight of the coating.
 12. The coated oral composition of claim 8, wherein the coated oral composition is selected from the group consisting of a chewing gum, a confection, a mint, a tablet, a bead, and a lozenge.
 13. A method of making a coated oral composition, the method comprising: pretreating MBE and LAE to form a preblend mixture; adding the preblend mixture to a coating syrup; and, applying the coating syrup to an oral composition to produce the coated oral composition.
 14. The method of claim 13, wherein the oral composition is selected from the group consisting of a chewing gum, a confection, a mint, a tablet, a bead, and a lozenge.
 15. The method of claim 13, wherein the MBE and LAE are pretreated by blending the MBE and LAE with one or more organoleptic components.
 16. The method of claim 13, wherein the coated oral composition comprises MBE and LAE in amounts that provide a synergistic reduction of the total salivary bacteria in an oral cavity of a consumer.
 17. The method of claim 13, wherein the weight ratio of MBE to LAE in the preblend mixture is from about 2:1 to about 1:2.
 18. The method of claim 13, wherein the MBE comprises from about 1% to about 2% by weight of the coating.
 19. The method of claim 13, wherein the LAE comprises from about 1% to about 2% by weight of the coating.
 20. The method of claim 13, wherein the coated oral composition is a coated chewing gum.
 21. The method of claim 13, wherein the MBE and LAE are pretreated by blending the MBE and LAE with a powdered gum base.
 22. The method of claim 13, wherein the MBE and LAE are pretreated by sieving the MBE and LAE.
 23. The method of claim 13, wherein the MBE and LAE are pretreated by pre-dissolving the MBE and LAE in a flavoring agent, glycerol, MCT oil, or combinations thereof.
 24. The method of claim 13, wherein the coated oral composition comprises MBE and LAE in amounts that provide a synergistic reduction of the total salivary bacteria in an oral cavity of a consumer.
 25. The method of claim 13, wherein the weight ratio of MBE to LAE in the preblend mixture is from about 2:1 to about 1:2. 